A major histocompatibility complex class Ib protein, CD1d, is expressed by human intestinal epithelial cells (IECs) and is a ligand for CD8(+) T cells. CD1d was found to be expressed on the surface of human IECs as a 37-kilodalton protein that was beta(2)-microglobulin (beta(2)M) independent with no N-linked carbohydrate. Transfection into a beta(2)M(-) cell line confirmed that CD1d could be expressed at the cell surface in the absence of beta(2)M. These data indicate that IECs use a specialized pathway for CD1d synthesis and that a beta(2)M-independent class Ib protein may be the normal ligand for some intestinal T cells.